Serum interleukin-18 levels as a predictor for patients with genetic dysfunction of cytochrome P450 2C19 in dual antiplatelet therapy with clopidogrel.

Background: P2Y reaction unit (PRU) is an index of platelet activity upon treatment with clopidogrel. In spite of suitable P2Y reactions in dual antiplatelet therapy (DAPT) with clopidogrel after percutaneous coronary intervention (PCI), cardiovascular events actually occur in some patients, possibly due to a genetic dysfunction of cytochrome P450 2C19 (CYP2C19), which is a major metabolic enzyme of clopidogrel. As testing the CYP2C19 phenotypes to predict such patients may lack general versatility in daily clinical practice, the aim of this study was to examine whether measuring the blood levels of some cytokines in patients showing desirable PRUs in DAPT with clopidogrel could be a substitute for testing the CYP2C19 phenotypes.

Methods: We analyzed relationships among PRU, serum levels of 51 cytokines, and CYP2C19 phenotypes in 22 patients receiving DAPT with aspirin and clopidogrel after PCI.

Results: Seventeen, 18, and 19 of 22 patients indicated PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively. Approximately 60% of the patients had a genetically metabolic dysfunction of CYP2C19, and the serum levels of interleukin-18 were independently increased in those patients (p = 0.024 in patients with PRU ≤ 208, p = 0.021 with PRU ≤ 230, and p = 0.020 with PRU ≤ 262). The area under the curves in plot receiver operating characteristics curves for the serum levels of interleukin-18 were 0.94, 0.96, and 0.90 in the non-extensive metabolizer patients with PRU ≤ 208, PRU ≤ 230, and PRU ≤ 262, respectively.

Conclusions: The serum levels of interleukin-18 may be a predictor to diagnose patients who receive undesirable DAPT with clopidogrel, possibly due to the genetic dysfunction of CYP2C19 in spite of suitable P2Y reactions after PCI.